It has been generally accepted that intravenous infusion, intramuscular injection, subcutaneous, buccal, oral, and rectal routes are the methods for administration of a wide variety of antimicrobial agents for the treatment of systemic bacterial diseases. Due to lack of systemic level effects with antimicrobial agents administered topically, the topical administration of antimicrobial agents has been limited to the treatment of localized infections of the skin or eyes.
However, it is known that the aforementioned non-topical methods of administration for the treatment of systemic bacterial diseases have certain disadvantages. For example, buccal and rectal administration often produce discomfort and aggravation to the mammals that are treated. The intravenous, subcutaneous and intramuscular routes are not only painful, but also must be performed by trained individuals. In addition, there is a risk of needle injury, infection, and other trauma including the emotional trauma inevitably associated with injections. Oral administration, although generally acceptable, may have the disadvantages of poor absorption of the therapeutic agent from the gastrointestinal tract and/or degradation which may be caused by the acidic medium of the stomach, or causes digestive disfunction in ruminants. Furthermore, in the case of treating animals, the aforementioned methods of administration are labor and time consuming. Topical administration of antimicrobial agents would circumvent these problems by allowing a more convenient, non-invasive method for the treatment of systemic bacterial diseases.
Thus, it is desirable to have antimicrobial agents that produce systemic effects when they are topically administrated for the treatment of systemic diseases.
It has been unexpectedly discovered, during the investigation of activities of antimicrobial agents by topical administration, that certain antimicrobial quinolones, such as premafloxacin, premafloxacin-like compound, ciprofloxacin, and enrofloxacin, and certain cephalosporin derivatives, such as cefquinome and cefpodoxime, as well as gentamicin and erythromycin, when administrated topically using dimethyl sulfoxide and water as a carrier, are effective for the treatment of systemic bacterial infections. It has also been discovered that premafloxacin, premafloxacin-like compound and its esters, when administrated topically using propylene glycol and oleyl alcohol or propylene glycol and Azone as a carrier, are effective for the treatment of systemic bacterial infections